Renewed attention has recently been focused on the role of fibrinogen in primary platelet aggregation. Numerous studies indicate that fibrinogen binding to human platelets is a prerequisite for aggregation. Since platelets serve a vital role in hemostasis and have been implicated in the pathogenesis of atherosclerosis and thrombosis, an investigation of the interrelationship between fibrinogen binding and platelet affregation is important. This will be accomplished by (1) further characterizing the interaction between purified 125-I-labeled fibrinogen and human gel filtered platelets in response to a variety of stimuli under conditions supporting and inhibiting aggregation, (2) analyzing fibrinogen binding (and possible alterations of the bound fibrinogen) throughout the various phases of aggregation including the release reaction and irreversible aggregation and (3) examining fibrinogen binding to platelets during the poorly understood "refractory" period induced by subaggregating doses of ADP. In addition, the role of platelet surface calcium in primary ADP-induced aggregation will be investigated by labeling platelet membrane calcium with 45-calcium and correlating calcium displacement with fibrinogen binding and platelet aggregability. Finally, the fibrinogen structural requirements for platelet binding will be explored by using fibrinogen derivatives isolated from human plasma or prepared in vitro by plasmin digestion which have well characterized alterations in the A Alpha, B Beta, and Gamma chains, and comparing their ability to bind to platelets and to support ADP-induced aggregation.